Pathological response after neoadjuvant therapy in soft tissue sarcoma: A systematic review of its association with local recurrence, distant metastasis, and survival.

Histopathological response after neoadjuvant therapy is an established prognostic marker in bone sarcoma, but its significance in soft tissue sarcoma remains uncertain. We systematically searched PubMed, Embase and CENTRAL through July 3, 2026 for studies evaluating the association between pathological response and oncological outcomes in adults undergoing neoadjuvant treatment and surgery for localized soft tissue sarcoma. Risk of bias was assessed using QUIPS and certainty of evidence using GRADE. Nineteen studies comprising 2346 unique patients were included. Pathological complete response rates ranged from 0% to 29%, with the highest observed pathological response frequencies in myxoid liposarcoma and undifferentiated pleomorphic sarcoma. Residual viable tumour and EORTC-STBSG response categories showed no reproducible association with outcomes. Necrosis was either non-prognostic or paradoxically associated with worse outcomes, possibly because it partly reflects inherent tumour aggressiveness. Fibrosis and hyalinization showed conflicting prognostic associations. Sclerohyalinosis greater than 20% was associated with improved disease-free survival in one prospective trial, but requires independent validation. GRADE certainty was low for pathological complete response and sclerohyalinosis and very low for necrosis and fibrosis/hyalinization. The prognostic value of pathological response in soft tissue sarcoma is therefore parameter-dependent. No pathological-response measure is sufficiently validated to guide routine management. Future pathological assessment should separately report viable tumour, necrosis, infarction, fibrosis/hyalinization and sclerohyalinosis and should undergo prospective, histotype-specific validation.